Hydrogen ventilation combined with mild hypothermia improves short-term neurological outcomes in a 5-day neonatal hypoxia-ischaemia piglet model.
新生児低酸素虚血性脳症ブタモデルにおける水素吸入と軽度低体温の併用による短期神経学的転帰の改善
Abstract
This animal study examined whether combining hydrogen gas inhalation with mild hypothermia could improve outcomes in a neonatal hypoxic-ischaemic encephalopathy (HIE) piglet model. Three groups were compared: normothermia, hypothermia alone (33.5 ± 0.5 °C), and hypothermia plus 2.1–2.7% H2 inhalation, each administered for 24 hours. Neurological assessments were conducted every 6 hours over 5 days post-weaning. Piglets receiving the combined intervention showed significantly higher neurological scores from day 3 onward compared with the normothermia group, and most regained walking ability by day 3. Histopathological analysis on day 5 revealed improved cortical gray matter and subcortical white matter integrity, along with a marked reduction in cell death, in the combination group. These findings suggest that H2 inhalation augments the neuroprotective effects of hypothermia in neonatal HIE.
Mechanism
H2 inhalation is proposed to complement hypothermia-mediated neuroprotection through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, collectively reducing neuronal cell death in cortical and subcortical regions.
Bibliographic
- Authors
- Htun Y, Nakamura S, Nakao Y, Mitsuie T, Nakamura M, Yamato S, et al.
- Journal
- Sci Rep
- Year
- 2019 (2019-03-11)
- PMID
- 30858437
- DOI
- 10.1038/s41598-019-40674-8
- PMC
- PMC6411734
Tags
Delivery context
In air, molecular hydrogen is reported to be combustible across approximately **4% (LFL, lower flammability limit) to 75% (UFL, upper flammability limit)**. Among high-concentration hydrogen inhalers, 66% output sits inside this range, and even pure-hydrogen (100%) output forms a 4–75% concentration-gradient layer at the device–air boundary (the UFL 75% paradox). Engineering principle would therefore call for operation below LFL (the classical 4%); that figure, however, was measured under closed, pre-mixed, static conditions. For the open, dynamic inhalation environment, the empirical value reported in the literature is **10%**, which is the figure referenced in practice as the operating ceiling. The 66% / 100% output devices are recorded in the Japanese Consumer Affairs Agency accident-information database, and from these considerations are not recommended.
Safety notes
See also: